AMX0114 in Adult Participants With Amyotrophic Lateral Sclerosis
ConditionALS
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAmylyx Pharmaceuticals Inc.
About this trial
This study is a placebo-controlled Phase I study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide (ASO) AMX0114 in adult participants with amyotrophic lateral sclerosis (ALS).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Ability to understand the purpose and risks of this study, willingness to comply with the study and to provide informed consent in accordance with local laws and regulations.
Male or female, at least 18 years of age.
Diagnosis of clinically definite or clinically probable ALS, made by a physician who is experienced with management of ALS.
Time since onset of first symptom of ALS should be <24 months prior to beginning the study. Date of ALS symptom onset is defined as the onset of weakness (in the limbs, bulbar region, or trunk).
Disqualifiers
Presence of tracheostomy or permanent assisted ventilation.
SVC less than 65%.
Abnormal liver function defined as aspartate aminotransferase and/or alanine aminotransferase > 3 times the upper limit of normal (ULN) and/or total bilirubin > 1.5 times the ULN (obtained within 4 weeks of first dose) except when a result of Gilbert syndrome.
Abnormal renal function defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2.
Trial design
Design model
Sequential
Treatments tested in this trial
AMX0114
DrugAntisense oligonucleotides (ASOs) are a type of medicine that treats diseases by intercepting the mRNA messages sent within the cell, resulting in fewer specific proteins being made. AMX0114 is an ASO that targets the mRNA messenger that instructs the body to create a protein called calpain-2. Calpain-2 has been linked to the degeneration and death of neurons in many neurological diseases, including people living with sporadic ALS. AMX0114 is designed to reduce the levels of calpain-2, with the goal of slowing down the process that leads to neuron injury and death.
Placebo
Other interventionPlacebo
Treatment groups
48 Participants
are divided into 2 treatment groupsGroup A: Active Treatment: AMX0114Experimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Evaluate the safety and tolerability of AMX0114 in adult participants living with ALS
Incidence of adverse events (AEs), serious adverse events (SAEs) and dose limiting toxicities (DLTs). Incidence of abnormalities in clinical laboratory assessments, vital signs, physical and neurological examinations, and electrocardiograms (ECGs).
Time frame
Day 1 - Day 145 (End of Study)Secondary outcomes
1
Evaluate the PK of AMX0114
Evaluate PK concentrations, including plasma and CSF levels of AMX0114
Time frame
Day 1 - Day 145 (End of Study)Other outcomes
1
Change from baseline at dosing days and end of study in CSF calpain-2 levels.
Time frame
Day 1 - Day 145 (End of Study)2
Change from baseline at dosing days and end of study in CSF and plasma NfL.
Time frame
Day 1 - Day 145 (End of Study)3
Change from baseline at dosing days and end of study in Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS - R).
The ALSFRS-R consists of 12 items across 4 subdomains of function (bulbar, fine motor, gross motor, and breathing) with each item scored on a scale from 0 (total loss of function) to 4 (no loss of function). Total scores range from 0 to 48, with higher scores indicating better function.
Time frame
Day 1 - Day 145 (End of Study)4
Change from baseline at dosing days and end of study in Slow Vital Capacity (SVC).
Time frame
Day 1 - Day 145 (End of Study)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Source ClinicalTrials.gov